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1、川崎病的诊治进展及其心血管并发症,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,2004 Dec.Beijing,川崎病定义,川崎病(Kawasaki Diseases,KD)又称皮肤粘膜淋巴结综合征(Mucocutaneous lymph node syndrome，MCLS)主要发生在5岁以下婴幼儿的急性发热出疹性疾病病因、发病机制不明发病时伴全身性血管炎，属血管炎综合征，所致冠状动脉并发症已经是最常见的儿童后天性心脏病,川崎病历史,自1967年日本医生川崎富作（Tomisaku Kawasaki)首次报道，日文文献;1961 至 1967 的50
2、例病例，皮肤黏膜淋巴结综合症；最初认为是一种良性疾病。,川崎病历史,1970年，Itsuzo Shigematsu等进行了日本第一次全国川崎病普查，结果10例2yr的患儿在症状好转时死亡；1976年美国Hawaii大学的Maria Melish在日本外首次报道了16例MCLS患儿，称Kawasaki Disease；在世界范围内都有报道，发病率逐年增高趋势。,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,60多个国家报道川崎病发生世界1/3的国家报道有川崎病,日本川崎病发病率改变,Nakamura Y,Yanagawa H.Prog Ped Cardi
3、ol,2004,19:99108,美国KD发病率报道资料,北京川崎病发病率,Du Zhong-Dong,et al.Pediatr Infect Dis J.2002,21(2):103107,预后,目前日本急性川崎病死亡率0.08%美国川崎病住院死亡率0.17%死亡多发生于发热后 1545天北京近10年急性死亡率0远期死亡因为冠状动脉并发症,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,病因及发病机制,感染因素 40年来很多学者筛选了无数种微生物的感染证据但到目前仍未找到明确的病因(coravirus):培养血清学动物接种,一种未知的RNA病毒(Ro
4、wley 2008)?可能的发病机制:川崎病是由一种或多种感染因素引起的一种强烈的免疫反应，这种反应只发生于本身基因有易感性的个体，如亚裔人群,发病机制,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,川崎病的六大主要表现,1、发烧持续5天以上(含经治疗5天以内退烧)2、双眼结膜充血3、口唇发红、草莓舌、口腔和咽喉粘膜充血4、多形性皮疹5、四肢末端变化，急性期手足硬性肿胀、掌 陌及指趾端充血；恢复期指趾端甲床皮肤 移行处有膜状脱皮6、急性期出现非化脓性颈部淋巴结肿胀,心脏病变,心外膜炎：发生率1517%；心肌炎：发生率约30%；大多数患儿没有症状，偶尔有
5、心包填塞或心功能不全；心内膜炎和/或二尖瓣返流：2.5%；多轻度，中度或重度1%;AR占0.2%；心律不齐,多数轻度、一过性。,超声心动图在川崎病诊治中的应用,协助川崎病的临床诊断不典型病人的诊断诊断心血管并发症心包炎、心包积液；瓣膜返流；心功能诊断冠状动脉并发症扩张，冠状动脉瘤冠状动脉内血栓诊断冠状动脉狭窄,超声诊断冠状动脉损害,冠状动脉瘤的好发部位：冠状动脉的起始部,顺序依次为：LAD近端、RCA近端、LMCA、LCX、RCA远端、RCA后降支。,体表面积校正的冠脉正常内径(Zorzi),ECHOCARDIOGRAPHY,冠状动脉瘤:定义：冠状动脉局部内径是其临近部位的 1.5倍;或者冠状
6、动脉内膜呈明显不规整。分型:小瘤：内径 8 mm,Echocardiogram of coronary RCA:右冠状动脉LCA:左冠状动脉Ao:主动脉,冠状动脉并发症发生率,未用IVIG治疗:20%男 24%，女15%（P0.001)IVIG治疗后:56%未用IVIG治疗冠状动脉瘤:4%IVIG治疗后:1%,日本川崎病冠状动脉并发症发生率改变,Males,Females,川崎病合并体循环瘤,时间：2003年12月1日2004年11月31日收住北京儿童医院心内科病房的全部川崎病患儿川崎病按照2002年日本小儿川崎病诊断标准第五次修订版作为诊断标准患儿入选前争得家长同意并签署知情同意书82例患儿
7、血管多普勒超声检查，1例发现双侧腋动脉瘤，发生率1.2%。,杜忠东，贾立群，张永兰等。中华儿科杂志,2007;45(5):395-396.,体循环瘤,18 x 9 x 11 mm,川崎病体循环瘤,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,川崎病治疗,急性期治疗(Primary therapy)：IVIGAsp激素？慢性期治疗溶栓介入性治疗搭桥手术,提要,定义和历史流行病学特点病因及发病机制临床表现及诊断标准治疗心血管并发症诊断及治疗,川崎病心血管并发症,冠状动脉病变短期冠状动脉扩张279/1409（19.8%）冠状动脉瘤313/2031（15.4）
8、IVIG 治疗后(1991-)60/676（8.9）体循环瘤21（1.0）心脏瓣膜病变 二尖瓣反流27（1.3）主动脉瓣反流5（0.2）心肌梗塞24（1.2）死亡 10（0.3）,(Kurume University 1973-2002,n=2031),冠状动脉瘤（北京）,48例冠状动脉瘤，发生率4.3%（95%CI,3.2%5.7%）4例巨大瘤，发生率为0.4%15例中动脉瘤，发生率1.4%29例小动脉瘤，发生率2.6%32例男性，16例女性（P=0.775）冠状动脉瘤发生率与年龄、起病年月、不同医院无关（P0.05）,RCA,LCA,第一次冠脉造影(发病40 d),RCA,LCA,第二次冠
9、脉造影(发病6个月,21个月男童(发病18个月),2000.4 2000.12 2002.3,冠脉狭窄及再通,64SCTCA,VR显示RCA全程迂曲扩张，部分呈串珠样改变，其中间插有狭窄段,64SCTCA,MPR显示RCA中段冠脉瘤，可见血栓和多发钙化灶,冠状动脉瘤的预后,Kato H,Akagi T,et al.Circulation 1996;94:1379,狭窄,回缩率（%）,狭窄率（%）,回缩,川崎病冠状动脉病变特点,50%CAL 2 年消退 血管中层平滑肌细胞增生，内膜增厚冠状动脉狭窄发生约占全部KD的4%，合并冠状动脉并发症患儿的20%没有报道冠状动脉扩张回复后发生冠状动脉狭窄？,
10、川崎病冠状动脉病变特点,儿童发病钙化发生率高多发病变，狭窄和瘤并存长期慢性进展(10-20 年)临床表现缺乏或不典型,冠状动脉狭窄或闭塞的治疗,药物:ASP,华法林？冠状动脉搭桥手术冠状动脉经导管介入性治疗其它?,Yoshikawa,et al.Eur J Cardio Surg 2000,1976年Kitamura首次报道自体隐静脉冠状动脉旁路移植手术(Kitamura S,Circulation，1976，53(6)：1035-1040)。,经导管介入性治疗,经皮腔内冠状动脉成形术（PTCA）冠状动脉内支架植入术 经皮腔内冠状动脉旋切术经皮腔内冠状动脉血运重建术,日本介入性治疗效果,经导管
11、介入性治疗的未来,干预的时间选择？治疗器械的选择提高远期效果：再狭窄新瘤形成治疗指导原则的建立与更新病人及家长的教育,川崎病冠状动脉并发症与冠脉粥样硬化的关系？,Sugimura T,Kato H,Inoue O,et al.The Journal of Pediatrics 1992;121.684-8,Cheung YF,Wong SJ,Ho MH.Archives of Disease in Childhood 2007;92:43-7,川崎病冠状动脉并发症与冠脉粥样硬化的关系？,KAWASAKI DISEASE AND ITS CORONARY COMPLICATION,Zhong-D
12、ong Du,MD,PhDProfessor of PediatricsBeijing Childrens HospitalCapital Medical University,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanismClinical pictures and diagnosisTreatmentLong-term management of coronary complication,DEFINITION,Kawasaki disease(KD)is an acute systemic
13、febrile illness predominantly affecting children 5 yrs of age.Initially described in Japan,KD has been reported worldwideKD is associated with coronary complication that might be life-threatening,and has become the leading cause of acquired heart diseaseMay be a risk factor for adult ischaemic heart
14、 disease Its etiology remains unknown.,BRIEF HISTORY,First described by Tomisaku Kawasaki in Japanese literature in 1967.He reported on 50 children who presented from 1961 to 1967 with symptoms distinct from other known childhood illnesses,and termed the disorder mucocutaneous lymph node syndrome.Or
15、iginally thought it was a benign self-limited disease.,BRIEF HISTORY,By late 1970,Itsuzo Shigematsu organized the first Japan nation wide KD Survey.Up to 10 deaths had occurred in children under age 2 years with KS in Japan.All the death was found to be caused by coronary aneurysm and thrombus in th
16、e coronary artery.In 1976,Melish described the same illness in 16 children in Hawaii.Reported world wide.,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanism Clinical pictures and diagnosisTreatmentLong-term management of coronary complication,60多个国家报道川崎病发生世界1/3的国家报道有川崎病,INCIDE
17、NCES OF KD IN JAPAN,Nakamura Y,Yanagawa H.Prog Ped Cardiol,2004,19:99108,INCIDENCES OF KD IN USA,INCIDENCE OF KD IN BEIJING,Du Zhong-Dong,et al.Pediatr Infect Dis J.2002,21(2):103107,MORTALITY,The case fatality rate in Japan is 0.08%.In US,in-hospital mortality rate is 0.17%.The peak mortality occur
18、s 15 to 45 days after the onset of fever.Acute mortality in Beijing is 0 for the last 10 years.Late mortality is due to the coronary aneurysm.,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanism Clinical pictures and diagnosisTreatmentLong-term management of coronary complicati
19、on,ETIOLOGY AND MECHANISM,Efforts to identify a conventional bacterial or virus infectious agent failed:CulturesSerological methodsAnimal inoculation,ETIOLOGY AND MECHANISM,Unknown RNA virus(Rowley 2008)?Possible mechanism:KD is caused by one or more infectious agents that produces clinically appare
20、nt disease only in certain genetically predisposed individuals,particularly Asians,by strong immune response.,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanism Clinical pictures and diagnosisTreatmentLong-term management of coronary complication,DIAGNOSTIC GUIDELINES,Principa
21、l symptomsFever persisting 5 days+Bilateral conjunctival congestionChanges of lips and oral cavityPolymorphous exanthemaChanges of peripheral extremitiesAcute nonprulent lymphadenopathy Diagnostic criteria with at least 5 items or 4 items+coronary aneurysms Other significant symptoms or findings,CAR
22、DIOVASCULAR FINDINGS,Cardiovascular manifestations can be prominent in the acute phase and are the leading cause of long-term morbidity and mortality.The pericardium,myocardium,endocardium,valves,and coronary arteries all may be involved.Cardiac auscultation:tachycardia,a gallop rhythm,and an flow m
23、urmur(anemia,fever,myocarditis,MR)Occasionally,poor myocardial function with low cardiac output syndrome or shock.ECG:arrhythmia,prolonged PR interval,or nonspecific ST and T wave changes.,ECHOCARDIOGRAPHY,Assisting diagnosis of KDIncomplete KDDiagnosis of cardiovascular complicationPericardial effu
24、sionVavular regurgitationCardiac functionDiagnosis of coronary complicationDilation,coronary aneurysmThrumbusCoronary stenosis,ECHOCARDIOGRAPHY,Coronary artery dilatation:Proximal CA:LMCA,LAD,RCAThe Japanese Ministry of Health criteria(1985):abnormal if the internal lumen diameter is 3 mm in childre
25、n 4 mm in children=5 years oldBeijing Childrens Hospital(1988):2.5 mm if age 3 mm if age 3-9 yr 4 mm if age 9yr,Normal Coronary Artery Diameter corrected by BSA(Zorzi),LCA,LCX,LAD,RCA,ECHOCARDIOGRAPHY,Coronary aneurysm:Definition:if the internal diameter of a segment measures 1.5 times that of an ad
26、jacent segment;or if the coronary lumen is clearly irregular.Classification:small 8-mm internal diameter,Echocardiogram of coronary RCA:right coronary arteryLCA:left coronary arteryAo:Aorta,RATES OF CORONARY COMPLICATIONS,Untreated children with KD:20%Boys 24%，Girl15%（P0.001)After IVIG treatment:56%
27、.Coronary aneurysm untreated pts:4%After IVIG:1%,PROPORTION OF PATIENTS WITH CARDIAC SEQUELAE,Males,Females,SYSTEMIC ARTERIAL ANEURYSM,2003/12/12004/11/31All children with KD admitted in Cardiology in-patient ward.Vascular ultrasound was performed with a high frequency linear probe.One in the 82 chi
28、ldren with KD had bilateral axillary aneurysm,with an incidence:1.2%。,SYSTEMIC ARTERIAL ANEURYSM,18 x 9 x 11 mm,Systemic Artery Aneurysms,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanism Clinical pictures and diagnosisTreatmentLong-term managemtn of coronary complication,TRE
29、ATMENT OF KD,Acute treatment：IVIGAspCorticosteriodsOther treatmentsChronic treatmentLong-term management of coronary complications,BRIEFS,Definition and historyEpidemiologic featuresEtiology and mechanism Clinical pictures and diagnosisTreatmentLong-term management of coronary complication,Cardiovas
30、cular Spectrum in KD,Coronary artery lesionsTransient dilatation279/1409（19.8%）Coronary aneurysm313/2031（15.4）IVGG treatment(since 1991)60/676（8.9）Systemic arterial aneurysms21（1.0）Valve lesionMitral insufficiency27（1.3）Aortic insufficiency5（0.2）Myocardial infarction24（1.2）Fatal cases10（0.3）,(Kurume
31、 University 1973-2002,n=2031),CORONARY ANEURYSM(BEIJING）,48 children in 5 yr,rate 4.3%（95%CI,3.2%5.7%）4 giant aneurysm，rate 0.4%15 medium，1.4%29 small，2.6%32 boy，16 girl（P=0.775）Rate not related to age,season,and hospital（P0.05）,RCA,LCA,1st Angiography(40 days after the onset),RCA,LCA,2nd Angiograph
32、y(6 months after the onset),21 months boy(18 months after the onset),2000.4 2000.12 2002.3,Coronary artery obstruction and recanalization,64SCTCA,RCA in VR,64SCTCA,RCA in MPR,Fate of Coronary Aneurysm,Kato H,Akagi T,et al.Circulation 1996;94:1379,Stenosis,%of Regression,%of progression to stenosis,R
33、egression,CLINICAL FEATURE OF CORONARY ARTERY LESION IN KD,About 50%of CAL regress 2 years.Intimal proliferation derived from the smooth muscle cells of media and regenerated endothelium.Coronary stenosis occurred in 4%of all patients,or in 20%with CAL in 10-22 years follow-up.No coronary stenosis h
34、as developed in 10-20 years follow-up in patients with regressed aneurysms.,CORONARY ARTERIAL LESION IN KD,Pediatric OnsetHigh Incidence of Calcified LesionMixed Lesions(Stenosis&Aneurysm)Progressive(10 to 20 years interval)Less Clinical Symptoms of Ischemia,TREATMENT OF CORONARY STENOSIS OR OCCLUSI
35、ON,Medicine:ASP,WarfarinCoronary by-pass surgeryTranscatheter interventionOther?,Yoshikawa,et al.Eur J Cardio Surg 2000,Kitamura first reported in 1976 in Japan(Kitamura S,Circulation，1976，53(6)：1035-1040)。,TRANSCATHETER INTERVENTIONS,Percutaneous transluminal coronary angioplasty(PTCA）Stent implant
36、ation Percutaneous transluminal coronary rotation ablation(PTCRA）Percutaneous transluminal coronay revascularization(PTCR）,RESULTS FROM JAPAN,FUTURE ISSUES OF CATHETER INTERVENTION,Optimal Timing of ProcedureOptimal Device SelectionLong-term Outcome(restenosis,neoaneurysm)Update of Therapeutic GuidelineEducation to Patients and Parents,CORONARY COMPLICATION AND LATE CORONARY ATHEROSCLEROSIS,Sugimura T,Kato H,Inoue O,et al.The Journal of Pediatrics 1992;121.684-8,CORONARY COMPLICATION AND LATE CORONARY ATHEROSCLEROSIS,Cheung YF,Wong SJ,Ho MH.Archives of Disease in Childhood 2007;92:43-7,
